The number of patients or pseudo-patients complaining of dry eye (dryness of the eyes) is expected to continue to climb as our society ages and as people increasingly strain their eyes by watching television and using office equipment such as word processors and personal computers. The cause of dry eye is a reduction in lacrimal quantity or a qualitative change in the components thereof, and this disorder can result in scratching or other damage when the surface of the eye becomes dry. Symptoms include eye pain or fatigue, increased blinking, and bloodshot eyes. Further, bacteria may enter through a scratch and cause infection, and if the scratch is deep enough it can even affect the vision of the person. In addition to eyestrain, causes of dry eye include Sjogren's syndrome, Stevens-Johnson syndrome, burns and injury to the eye, and side effects of hypotensive drugs, tranquilizers, eyedrops for treating glaucoma, and other such drugs.
Eyedrops are an effective way to treat dry eye, and dry-eye treatment drugs whose main component is hyaluronic acid are currently attracting much attention and are widely used. Hyaluronic acid is a biologically derived macromolecular substance, has extremely high water retention and characteristic properties such as a high viscoelasticity, a good thickening property, and a good thread-forming, ability, and has been used as a humectant in topical agents for treating various kinds of skin problems and so forth. In the case of dry eye caused by Sjogren's syndrome, in which dryness is seen over' the entire body, the application of eyedrops containing hyaluronic acid is effective all by itself, but when the symptoms are severe, hyaluronic acid-containing eyedrops alone may not provide a sufficient effect, and it is sometimes necessary for the treatment to entail tear duct blockage by means of a tear duct plug. Also, hyaluronic acid has a relatively short residence time on the cornea, so the effect of hyaluronic acid eyedrops lasts only about 2 or 3 hours, which means that the patient must apply the drops more frequently (such as 5 to 10 times a day). There is therefore a need for an ophthalmic pharmaceutical composition that would provide a long-lasting humectant effect, and therefore require fewer applications and improve the QOL (quality of life) of the patient.
Japanese Laid-Open Patent Application S62-68402 discloses a derivative of hyaluronic acid, namely, a hyaluronic acid that has undergone partial esterification of its carboxyl groups, and suggests that this derivative is effective as a drug carrier. However, it has yet to be confirmed that an ophthalmic preparation containing this carboxyl group partially esterified hyaluronic acid derivative as a carrier is effective in pharmaceutical compositions used for dry eye, which must provide a long-lasting humectant effect.